Is acetaminophen really safe in pregnancy?

With up to 70 percent of pregnant American women reaching for acetaminophen to treat pain, infection, and fever, debate about the drug's safety is ongoing. New research has brought further risks to light.

Acetaminophen is generally regarded as safe during pregnancy, but more evidence pointing to the contrary is coming to light.

The Food and Drug Administration (FDA) always recommend consulting a doctor prior to using any pain medication during pregnancy.

Acetaminophen — also known as paracetamol — is a widely available over-the-counter (OTC) painkiller, used by 65–70 percent of pregnant women in the United States.

But it is also a component of many other drugs, such as those used to treat symptoms of the common cold or flu, allergies, and sleep problems.

Research into the drug's safety during pregnancy is ongoing, with little in the way of definitive conclusions. The FDA point out that "severe and persistent pain that is not effectively treated during pregnancy can result in depression, anxiety, and high blood pressure in the mother."

"However, it is important to carefully weigh the benefits and risks of using prescription and OTC pain medicines during pregnancy," the statement continues.

As an expectant mother myself, I've been keeping a close eye on any studies into the drug's effect. Evidence of a link between attention deficit and hyperactivity disorder (ADHD) and the use of acetaminophen during pregnancy has been steadily mounting over the past few years.

In the past week, two new studies have joined the ranks, and they point to the potential effects on fertility and language development after acetaminophen use.

Here is what you need to know.

ADHD and behavioral problems

While there have been many efforts in the past to untangle a possible link between ADHD and acetaminophen use, the FDA have been critical of many of these.

According to their latest statement, from 2015, "[W]e found all of the studies we reviewed to have potential limitations in their designs; sometimes the accumulated studies on a topic contained conflicting results that prevented us from drawing reliable conclusions."

Last November, we brought you a study from the journal Pediatrics that asked nearly 100,000 mothers about their acetaminophen use during pregnancy.

Almost half of the participants had used the drug. The researchers revealed that the risk of having a child with ADHD symptoms significantly increased when mothers took acetaminophen for more than 7 days.

Use of the drug for 29 days or longer doubled the risk of having a child with ADHD, regardless of whether the reason for taking the OTC drug was fever, infection, or pain.

These results are in line with a study we covered in 2016 that showed that acetaminophen use was linked to behavioral problems. The team — from the University of Bristol and Cardiff University, both in the United Kingdom — found that when mothers took acetaminophen at 18 weeks of pregnancy, their children were more likely to have conduct problems and symptoms of hyperactivity.

When the drug was used later on in pregnancy — at 32 weeks — these same traits were observed, but the risk of emotional symptoms and total behavioral difficulties was also higher.

New research published in the past week further incriminates acetaminophen, but this time, the effects are on fertility and language development.

Fertility affected across generations

A few years ago, we reported on a study that showed a potential link between acetaminophen use and fertility problems in male offspring in a mouse model.

The research team — from the University of Edinburgh in the U.K. — showed that three daily doses of acetaminophen over 7 days caused the levels of testosterone in male mouse babies to drop by nearly half.

Last week, a review of studies looking at the effects of acetaminophen use and fertility in female offspring concluded that the last weeks of the first trimester may be a critical time window.

Data obtained from rodent studies indicate that acetaminophen may disrupt normal development of the female reproductive organs, causing symptoms similar to premature ovarian insufficiency syndrome in humans.

Data from three independent studies, cited in the review, revealed that when rodents received acetaminophen, their offspring produced fewer eggs.

What is more, in one of the studies, this was passed on to the next generation, even if no more exposure to acetaminophen took place.

Senior paper author David Møbjerg Kristensen, Ph.D. — an assistant professor at the University of Copenhagen in Denmark — says, "[A]lthough this may not be a severe impairment to fertility, it is still of real concern since data from three different labs all independently found that paracetamol may disrupt female reproductive development in this way, which indicates further investigation is needed to establish how this affects human fertility."

Prof. Kristensen urges that further research is needed.

"[...] by combining epidemiological data from human studies with more experimental research on models, such as rodents, it may be possible to firmly establish this link and determine how it happens, so that pregnant women in pain can be successfully treated, without risk to their unborn children."

Prof. David Møbjerg Kristensen

Acetaminophen and language delay

A new study — published just yesterday — adds another dimension to the potential hazards that acetaminophen may cause.

Shanna Swan, Ph.D. — who is a professor of environmental and public health at the Icahn School of Medicine at Mount Sinai in New York City, NY — and team studied early language development in children whose mothers took acetaminophen during the very early stages of pregnancy.

Writing in the journal European Psychiatry, Prof. Swan used data from the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy study.

This included self-reported data on acetaminophen use in early pregnancy — meaning between the point of conception and enrolment in the study, which typically occurred at 8–13 weeks of pregnancy.

The data also included a measurement of acetaminophen levels in the urine of all participants at enrolment. The results found that 59 percent of the 754 women in the study took acetaminophen during early pregnancy.

Language delay in children — meaning the use of fewer than 50 words by the age of 30 months — was assessed by specialist nurses and a follow-up questionnaire. The authors also explain in the paper that it is "an early marker of impaired cognitive development."

In all, 10 percent of the children experienced language delay. This was greater in boys than in girls.

However, when mothers took six or more tablets of acetaminophen during early pregnancy, the risk of their daughters showing signs of language delay was increased by almost six times.

Acetaminophen use was not linked to language delay in boys in this study.

Commenting on the findings, Prof. Swan states, "[G]iven the prevalence of prenatal acetaminophen use and the importance of language development, our findings, if replicated, suggest that pregnant women should limit their use of this analgesic during pregnancy."

"It's important for us to look at language development," she adds, "because it has shown to be predictive of other neurodevelopmental problems in children."

Is acetaminophen safe?

Unfortunately, there's no simple answer. The majority of studies do not show any long-term effects if acetaminophen is taken sporadically and at low doses. However, as few as six tablets taken in early pregnancy increases the risk of language delay in daughters.

For some expectant mothers, longer use of acetaminophen is the only way to deal with severe pain or fever and infections, which can cause potential harm to their unborn baby if untreated. It can be a fine balancing act between risk and benefit.

The FDA make their views clear: work with your healthcare professional and take acetaminophen only when it is recommended.

In the meantime, expectant mothers like me will have to wait and see what research brings to light, to help inform our future choices.

2018 Healthline Media UK Ltd. All rights reserved. MNT is the registered trade mark of Healthline Media. Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a healthcare professional.